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Toll-like Interleukin 1 Receptor Regulator Is an Important Modulator of Inflammation Responsive Genes

Authors :
Mohammad Abul Kashem
Hongzhao Li
Nikki Pauline Toledo
Robert Were Omange
Binhua Liang
Lewis Ruxi Liu
Lin Li
Xuefen Yang
Xin-Yong Yuan
Jason Kindrachuk
Francis A. Plummer
Ma Luo
University of Manitoba
Source :
Frontiers in Immunology, Frontiers in Immunology, Vol 10 (2019)
Publication Year :
2019
Publisher :
Frontiers Media SA, 2019.

Abstract

TILRR (Toll-like interleukin-1 receptor regulator), a transcript variant of FREM1, is a novel regulatory component, which stimulates innate immune responses through binding to IL-1R1 (Interleukin-1 receptor, type 1) and TLR (Toll-like receptor) complex. However, it is not known whether TILRR expression influences other genes in the NFκB signal transduction and pro-inflammatory responses. Our previous study identified FREM1 as a novel candidate gene in HIV-1 resistance/susceptibility in the Pumwani Sex worker cohort. In this study, we investigated the effect of TILRR overexpression on expression of genes in the NFκB signaling pathway in vitro. The effect of TILRR on mRNA expression of 84 genes related to NFκB signal transduction pathway was investigated by qRT-PCR. Overexpression of TILRR on pro-inflammatory cytokine/chemokine(s) secretion in cell culture supernatants was analyzed using Bioplex multiplex bead assay. We found that TILRR overexpression significantly influenced expression of many genes in HeLa and VK2/E6E7 cells. Several cytokine/chemokine(s), including IL-6, IL-8 (CXCL8), IP-10, MCP-1, MIP-1β, and RANTES (CCL5) were significantly increased in the cell culture supernatants following TILRR overexpression. Although how TILRR influences the expression of these genes needs to be further studied, we are the first to show the influence of TILRR on many genes in the NFκB inflammatory pathways. The NFκB inflammatory response pathways are extremely important in microbial infection and pathogenesis, including HIV-1 transmission. Further study of the role of TILRR may identify the novel intervention targets and strategies against HIV infection.

Details

ISSN :
16643224
Volume :
10
Database :
OpenAIRE
Journal :
Frontiers in Immunology
Accession number :
edsair.doi.dedup.....46891e90f4bb8bbc071ac5a919a7ae12
Full Text :
https://doi.org/10.3389/fimmu.2019.00272